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O14493

- CLD4_HUMAN

UniProt

O14493 - CLD4_HUMAN

Protein

Claudin-4

Gene

CLDN4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 125 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    Plays a major role in tight junction-specific obliteration of the intercellular space.By similarity

    GO - Molecular functioni

    1. identical protein binding Source: UniProtKB
    2. structural molecule activity Source: InterPro
    3. transmembrane signaling receptor activity Source: ProtInc

    GO - Biological processi

    1. calcium-independent cell-cell adhesion Source: UniProtKB
    2. establishment of skin barrier Source: UniProtKB
    3. female pregnancy Source: Ensembl
    4. response to progesterone Source: Ensembl
    5. signal transduction Source: GOC

    Enzyme and pathway databases

    ReactomeiREACT_19373. Tight junction interactions.

    Protein family/group databases

    TCDBi1.H.1.1.6. the claudin tight junction (claudin) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Claudin-4
    Alternative name(s):
    Clostridium perfringens enterotoxin receptor
    Short name:
    CPE-R
    Short name:
    CPE-receptor
    Williams-Beuren syndrome chromosomal region 8 protein
    Gene namesi
    Name:CLDN4
    Synonyms:CPER, CPETR1, WBSCR8
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:2046. CLDN4.

    Subcellular locationi

    Cell junctiontight junction By similarity. Cell membrane By similarity; Multi-pass membrane protein By similarity

    GO - Cellular componenti

    1. apical plasma membrane Source: Ensembl
    2. apicolateral plasma membrane Source: Ensembl
    3. basal plasma membrane Source: Ensembl
    4. integral component of plasma membrane Source: UniProtKB
    5. lateral plasma membrane Source: Ensembl
    6. plasma membrane Source: ProtInc
    7. tight junction Source: UniProtKB

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Membrane, Tight junction

    Pathology & Biotechi

    Involvement in diseasei

    CLDN4 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi208 – 2081Y → F: Loss of phosphorylation by EPHA2. 1 Publication

    Keywords - Diseasei

    Williams-Beuren syndrome

    Organism-specific databases

    PharmGKBiPA26572.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 209209Claudin-4PRO_0000144743Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei208 – 2081Phosphotyrosine; by EPHA21 Publication

    Post-translational modificationi

    Phosphorylated. Phosphorylation by EPHA2 is stimulated by EFNA1 and alters interaction with TJP1.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO14493.
    PaxDbiO14493.
    PRIDEiO14493.

    PTM databases

    PhosphoSiteiO14493.

    Expressioni

    Gene expression databases

    ArrayExpressiO14493.
    BgeeiO14493.
    CleanExiHS_CLDN4.
    GenevestigatoriO14493.

    Organism-specific databases

    HPAiCAB002610.
    HPA007322.

    Interactioni

    Subunit structurei

    Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3. Interacts with EPHA2; phosphorylates CLDN4 and may regulate tight junctions.1 Publication

    Protein-protein interaction databases

    BioGridi107756. 2 interactions.
    IntActiO14493. 1 interaction.
    STRINGi9606.ENSP00000342445.

    Structurei

    3D structure databases

    ProteinModelPortaliO14493.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 77CytoplasmicSequence Analysis
    Topological domaini29 – 8153ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini103 – 11715CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini139 – 16022ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini182 – 20928CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei8 – 2821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei82 – 10221HelicalSequence AnalysisAdd
    BLAST
    Transmembranei118 – 13821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei161 – 18121HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 103103Interaction with EPHA2Add
    BLAST
    Regioni208 – 2092Interactions with TJP1, TJP2 and TJP3By similarity

    Sequence similaritiesi

    Belongs to the claudin family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG46413.
    HOGENOMiHOG000220937.
    HOVERGENiHBG000643.
    InParanoidiO14493.
    KOiK06087.
    OMAiTAHNVIR.
    OrthoDBiEOG79KPGQ.
    PhylomeDBiO14493.
    TreeFamiTF331936.

    Family and domain databases

    InterProiIPR006187. Claudin.
    IPR003550. Claudin4.
    IPR017974. Claudin_CS.
    IPR004031. PMP22/EMP/MP20/Claudin.
    [Graphical view]
    PANTHERiPTHR12002. PTHR12002. 1 hit.
    PfamiPF00822. PMP22_Claudin. 1 hit.
    [Graphical view]
    PRINTSiPR01077. CLAUDIN.
    PR01379. CLAUDIN4.
    PROSITEiPS01346. CLAUDIN. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O14493-1 [UniParc]FASTAAdd to Basket

    « Hide

    MASMGLQVMG IALAVLGWLA VMLCCALPMW RVTAFIGSNI VTSQTIWEGL    50
    WMNCVVQSTG QMQCKVYDSL LALPQDLQAA RALVIISIIV AALGVLLSVV 100
    GGKCTNCLED ESAKAKTMIV AGVVFLLAGL MVIVPVSWTA HNIIQDFYNP 150
    LVASGQKREM GASLYVGWAA SGLLLLGGGL LCCNCPPRTD KPYSAKYSAA 200
    RSAAASNYV 209
    Length:209
    Mass (Da):22,077
    Last modified:January 1, 1998 - v1
    Checksum:i0659A93AA5F0E4C5
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB000712 mRNA. Translation: BAA22984.1.
    BT006989 mRNA. Translation: AAP35635.1.
    BC000671 mRNA. Translation: AAH00671.1.
    CCDSiCCDS5560.1.
    RefSeqiNP_001296.1. NM_001305.4.
    UniGeneiHs.647036.
    Hs.729359.

    Genome annotation databases

    EnsembliENST00000340958; ENSP00000342445; ENSG00000189143.
    ENST00000431918; ENSP00000388639; ENSG00000189143.
    ENST00000435050; ENSP00000409544; ENSG00000189143.
    GeneIDi1364.
    KEGGihsa:1364.
    UCSCiuc003tzi.4. human.

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB000712 mRNA. Translation: BAA22984.1 .
    BT006989 mRNA. Translation: AAP35635.1 .
    BC000671 mRNA. Translation: AAH00671.1 .
    CCDSi CCDS5560.1.
    RefSeqi NP_001296.1. NM_001305.4.
    UniGenei Hs.647036.
    Hs.729359.

    3D structure databases

    ProteinModelPortali O14493.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107756. 2 interactions.
    IntActi O14493. 1 interaction.
    STRINGi 9606.ENSP00000342445.

    Protein family/group databases

    TCDBi 1.H.1.1.6. the claudin tight junction (claudin) family.

    PTM databases

    PhosphoSitei O14493.

    Proteomic databases

    MaxQBi O14493.
    PaxDbi O14493.
    PRIDEi O14493.

    Protocols and materials databases

    DNASUi 1364.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000340958 ; ENSP00000342445 ; ENSG00000189143 .
    ENST00000431918 ; ENSP00000388639 ; ENSG00000189143 .
    ENST00000435050 ; ENSP00000409544 ; ENSG00000189143 .
    GeneIDi 1364.
    KEGGi hsa:1364.
    UCSCi uc003tzi.4. human.

    Organism-specific databases

    CTDi 1364.
    GeneCardsi GC07P073213.
    HGNCi HGNC:2046. CLDN4.
    HPAi CAB002610.
    HPA007322.
    MIMi 602909. gene.
    neXtProti NX_O14493.
    PharmGKBi PA26572.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG46413.
    HOGENOMi HOG000220937.
    HOVERGENi HBG000643.
    InParanoidi O14493.
    KOi K06087.
    OMAi TAHNVIR.
    OrthoDBi EOG79KPGQ.
    PhylomeDBi O14493.
    TreeFami TF331936.

    Enzyme and pathway databases

    Reactomei REACT_19373. Tight junction interactions.

    Miscellaneous databases

    ChiTaRSi CLDN4. human.
    GeneWikii CLDN4.
    GenomeRNAii 1364.
    NextBioi 5527.
    PROi O14493.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O14493.
    Bgeei O14493.
    CleanExi HS_CLDN4.
    Genevestigatori O14493.

    Family and domain databases

    InterProi IPR006187. Claudin.
    IPR003550. Claudin4.
    IPR017974. Claudin_CS.
    IPR004031. PMP22/EMP/MP20/Claudin.
    [Graphical view ]
    PANTHERi PTHR12002. PTHR12002. 1 hit.
    Pfami PF00822. PMP22_Claudin. 1 hit.
    [Graphical view ]
    PRINTSi PR01077. CLAUDIN.
    PR01379. CLAUDIN4.
    PROSITEi PS01346. CLAUDIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo."
      Katahira J., Sugiyama H., Inoue N., Horiguchi Y., Matsuda M., Sugimoto N.
      J. Biol. Chem. 272:26652-26658(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Fetal brain.
    2. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Colon.
    4. "EphA2 phosphorylates the cytoplasmic tail of Claudin-4 and mediates paracellular permeability."
      Tanaka M., Kamata R., Sakai R.
      J. Biol. Chem. 280:42375-42382(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH EPHA2 AND TJP1, MUTAGENESIS OF TYR-208, PHOSPHORYLATION AT TYR-208 BY EPHA2.
    5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiCLD4_HUMAN
    AccessioniPrimary (citable) accession number: O14493
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 125 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3